Research Assistant The University of Chicago Chicago, Illinois, United States
Background: Chronic NSAID use increases risk for gastric side effects, and impaired metabolism via CYP2C9 may increase this risk. We hypothesized that patients (pts) carrying ≥1 loss-of-function allele (intermediate/poor metabolizers: IM/PM) are at higher risk for experiencing gastric toxicity. Methods: Using real-world observational data between 2010-20, we retrospectively analyzed pharmacogenomic study pts who were genotyped for CYP2C9 for reasons unrelated to NSAID prescribing. We defined chronic NSAID users as pts who had multiple NSAID (celecoxib, diclofenac, flurbiprofen, ibuprofen, meloxicam) prescriptions over a ≥120 day period. All others were defined as controls. Using ICD codes, serious gastric events were defined as ulcers, non-alcoholic gastritis or duodenitis; gastric toxicity was defined as serious gastric events, GERD or esophagitis. To compare risk between groups, we used odds ratios and performed two-sided t-tests. Results: Of 606 CYP2C9-genotyped pts (median age 64.9; 30.9% White, 63.4% Black; avg 3.5±2.5 observation years), 129 were chronic NSAID users and 471 were controls. Normal metabolizers (NM) = 460 (75.9%), IMs = 131 (21.6%), PMs = 15 (2.5%). Notably, 58.1% of chronic NSAID users experienced gastric toxicity compared to 46.7% of controls (OR 1.6, 95% CI 1.1-2.4, p=0.03). IM/PMs had increased serious gastric event rates (5/35 = 14.3% IM/PM vs 10/94 = 10.63% NM) and gastric toxicity (21/35 = 60% IM/PM vs 54/94 = 57.4% NM), although neither difference reached statistical significance. Conclusion: Chronic NSAID use increases gastric risk, which may be even higher in pts with impaired CYP2C9 metabolism, although significant differences between phenotypic groups were not observed. Larger cohorts should be examined to further determine whether CYP2C9 should be considered when prescribing NSAIDs.
